2006年9月
Role of type II topoisomerase mutations and AcrAB efflux pump in fluoroquinolone-resistant clinical isolates of Proteus mirabilis
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
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- 巻
- 58
- 号
- 3
- 開始ページ
- 673
- 終了ページ
- 677
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/jac/dkl297
- 出版者・発行元
- OXFORD UNIV PRESS
Objectives: We conducted a study to determine the role played by amino acid mutations in DNA gyrase and topoisomerase IV, and the AcrAB efflux pump in resistance to fluoroquinolones in clinical isolates of Proteus mirabilis.
Methods: Nine clinical isolates of P. mirabilis containing eight fluoroquinolone-resistant isolates and one fluoroquinolone-susceptible isolate as the causative pathogen were collected from different patients with urinary tract infections. Fluoroquinolone resistance was characterized by PCR and DNA sequencing. The role of the AcrAB efflux pump was investigated by semi-quantifying the transcriptional expression of the acrB gene.
Results: Double mutations were found in GyrA, at S83I and E87K, and single mutations in GyrB (S464F) and ParC (S80I) in four isolates with ciprofloxacin MICs of 16 to > 128 mg/L. In three isolates (ciprofloxacin MICs of > 128 mg/L), the level of acrB expression was 2.1- to 3.2-fold higher than that in the wild-type control strain (ciprofloxacin MIC of <= 0.12 mg/L) and these isolates also had increased MICs of minocycline (> 64 versus 8-16 mg/L) and chloramphenicol (> 256 versus 4-8 mg/L) compared with the five other fluoroquinolone-resistant isolates.
Conclusion: Our findings demonstrate that two mechanisms-mutations in GyrA (at S83I and E87K), GyrB and ParC, and overproduction of the AcrAB efflux pump-might synergistically contribute to a highest level of resistance to fluoroquinolones in clinical isolates of P. mirabilis.
Methods: Nine clinical isolates of P. mirabilis containing eight fluoroquinolone-resistant isolates and one fluoroquinolone-susceptible isolate as the causative pathogen were collected from different patients with urinary tract infections. Fluoroquinolone resistance was characterized by PCR and DNA sequencing. The role of the AcrAB efflux pump was investigated by semi-quantifying the transcriptional expression of the acrB gene.
Results: Double mutations were found in GyrA, at S83I and E87K, and single mutations in GyrB (S464F) and ParC (S80I) in four isolates with ciprofloxacin MICs of 16 to > 128 mg/L. In three isolates (ciprofloxacin MICs of > 128 mg/L), the level of acrB expression was 2.1- to 3.2-fold higher than that in the wild-type control strain (ciprofloxacin MIC of <= 0.12 mg/L) and these isolates also had increased MICs of minocycline (> 64 versus 8-16 mg/L) and chloramphenicol (> 256 versus 4-8 mg/L) compared with the five other fluoroquinolone-resistant isolates.
Conclusion: Our findings demonstrate that two mechanisms-mutations in GyrA (at S83I and E87K), GyrB and ParC, and overproduction of the AcrAB efflux pump-might synergistically contribute to a highest level of resistance to fluoroquinolones in clinical isolates of P. mirabilis.
- リンク情報
- ID情報
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- DOI : 10.1093/jac/dkl297
- ISSN : 0305-7453
- PubMed ID : 16870650
- Web of Science ID : WOS:000239902500031